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DIABETES 

At recruitment, nearly half of women and a third of men aged 50-59 had obesity (ie, had a BMI ≥30 kg/m2) and by age 60 more than one in five had a confirmed diagnosis of diabetes. Those with diabetes had four times the overall death rate at ages 35-74 compared with people without diabetes.  The excess mortality among people with diabetes accounted for at least one-third of all deaths between the ages 35-74 years, which is twice that suggested by previous studies. Read full paper.

The biggest excess risk of death among people with diabetes was from kidney disease, followed by heart and other vascular disease, infection and acute diabetic crises. Subsequent analyses revealed the types of infection most strongly related to diabetes. Read full paper.

OBESITY

Obesity makes diabetes and several other chronic diseases more common, but these diseases can cause substantial weight loss, thereby hiding their initial cause. To try to counteract this concealment we looked at the association between obesity and mortality more than five years after recruitment and excluded people who had chronic disease at recruitment. We found that general obesity, as well as carrying excess fat around the waist, were major risk factors for premature death. Among those with BMI>25 kg/m2, each increase of 5 kg/m2 was associated with a 30% increase in mortality. Waist circumference was particularly strongly related to mortality suggesting that abdominal obesity is especially harmful. Read full paper.

By measuring nuclear magnetic resonance (NMR) blood biomarkers we found positive associations between both higher total fat and higher abdominal fat with numerous molecules in the blood that are linked to type 2 diabetes and heart disease. Conversely, higher hip and upper thigh fat were associated with a favourable NMR metabolic profile. Read full paper. 

BMI is the sum of Fat Mass Index (FMI) and Lean Mass Index (LMI). We found that FMI and LMI had independent but opposite associations with death from vascular and metabolic causes. This suggests that using BMI alone to assess disease risk may be less informative than using FMI and LMI. Read full paper. 

BMI was strongly associated with death due to COVID-19 in 2020. However, even in 2020 other causes of death accounted for more than twice as many deaths as COVID-19, so the absolute effect of BMI on mortality was still greater for the aggregate of those other causes than for COVID-19. Read full paper.

SMOKING AND CAUSE-SPECIFIC MORTALITY

Smoking a few cigarettes a day – ‘low intensity smoking’ - was associated with increased mortality, particularly from respiratory cancers, chronic obstructive pulmonary disease and gastrointestinal and vascular diseases. Of those smoking an average of about 10 cigarettes per day, about one third were killed by their habit. However, as in other populations, quitting substantially reduced these risks. Read full paper.

BLOOD PRESSURE 

Blood pressure was a major risk factor for death from a range of diseases. It was especially strongly related to death from vascular and kidney disease, with no ‘threshold’ levels below which lower blood pressure was not associated with lower risk. As those with diabetes were at substantially higher risk than those without diabetes, the mortality rates associated with elevated blood pressure were much higher in these individuals. Read full paper.

SOCIOECONOMIC STATUS

Participants with no formal education had about twice the mortality rate of participants with tertiary level education, resulting in an average reduction in life expectancy of approximately six years. Lifestyle factors such as smoking, alcohol drinking, and leisure time physical activity and the related physiological correlates of obesity, diabetes, and high blood pressure accounted for about four-fifths of the association of education with premature death. Read full paper.

GENETIC ANALYSES

People with Latino ethnic background are under represented in genetic research. Through an academic-industry partnership with the  Regeneron Genetics Center® and AstraZeneca we generated genotype and exome data for the whole cohort, and whole-genome sequencing data for a subset of 9,950 participants. This is one of the most extensive sequencing studies of individuals from non-European ancestry and a major step forward for diversity in genetic research. Read full paper and press release.

These data have already contributed to several new discoveries:

  • Combining MCPS data with data from a further 500,000 people in the UK and the US led to the discovery of rare genetic variations in the GPR75 gene that were associated with protection against obesity. Read full paper  and press release.
  • Variants in the MAP3K15 gene were shown to protect against diabetes. The protective effect was stronger in individuals who did not carry the Latino-enriched SLC16A11 risk haplotype. Read full paper.
  • Truncations of the gene INHBE were associated with favourable fat distribution, favourable metabolic profile and protection from diabetes. Read full paper.
  • Rare loss-of-function mutations in the CHRNB2 gene were associated with a reduced likelihood of heavy smoking. Read full paper.

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